PATHOGENESIS OF IDIOPATHIC IGA NEPHROPATHY

Despite a prodigious amount of work on the physiology of IgA productio n in man, and many studies on the immunopathology of IgA nephropathy, ranging from the immunogenetics to the immune response to chemical cha racteristics of the IgA, we are hardly any nearer to defining the path ogenesis of this disease. One of the main changes in our understanding has been to recognise that the bone marrow, now known to produce norm ally one-third of the body's IgA, overproduces this immunoglobulin in IgA nephropathy. This alters the previous notion that IgA nephropathy was due simply to IgA production in the mucosa, although a mucosal com ponent is not excluded. Certain characteristics of the IgA in the dise ased kidney and the circulation have been defined: it is of subclass I gA 1 and has a higher proportion of lambda light chains and negative c harge than in normal subjects. The specificities of the IgA, either in the kidney or in complexes, have not helped to clarify the pathogenes is. They have been found for a wide range of endogenous and exogenous antigens, suggesting that the antibody activity represents polyclonal B cell activation. These findings have not helped to confirm the preva iling theory that IgA nephropathy is an immune complex disease. Other theories put forward are that IgA nephropathy is an autoimmune disease , glomerular components or IgA itself being among the candidate antige ns, or that there is primary dysregulation of the IgA immune system. A t this stage of development in our understanding of this common nephro pathy, it is important to guard against the assumption that idiopathic IgA nephropathy is one disease and is the result of a single pathogen etic mechanism.